Genotype-phenotype relationships in fragile X families

Fragile X syndrome is one of a group of conditions called trinucleotide repeat disorders, in which a pattern of three DNA nucleotides (CGG in this case) is repeated several times. These conditions are often caused by a gene change that begins with a premutation (with fewer repetitions of the pattern) and then expands to a full mutation in subsequent generations. This study explores both the neurodevelopmental and neurodegenerative effects of the premutation in both children (ages 8-16) and adults (over age 40) with the premutation (55-200 CGG repeats). A cohort of 500 adults and 150 children will be evaluated by a detailed neurological examination and a quantitative measurement of movement problems. In addition, psychiatric measures, neuropsychological testing, and magnetic resonance imaging (MRI) will be used to assess involvement in carriers of the mutation. These studies will enhance understanding of the premutation phenotype.